In recent years, a patch containing a so-called systemically active drug, such as tulobuterol (bronchial asthma therapeutic agent), fentanyl (persistent cancer pain therapeutic agent), rivastigmine (Alzheimer disease therapeutic agent), and oxybutynin (overactive bladder therapeutic agent), has been commercially available, and used in a clinical setting.
The patch containing the systemically active drug has such characteristics that the constant blood level of the drug can be maintained for an extended period. Therefore, a patch that can be administered once daily and a patch that can be administered for a period as long as one week have been developed.
From the viewpoints of solubility of the drug and a base ingredient, drug releasability from the base ingredient, stable adherence in long-term administration, or the like, most of the patches may be provided as a so-called tape having a base such as an acrylic adhesive, a silicone-based adhesive, and a styrene-isoprene-styrene block copolymer as a main material.
For stable administration of the drug over an extended period, the mixing amount and the crystalline form of the drug in a patch, and an interaction of the drug and the patch base such as actions of the drug and the base ingredient have been conventionally investigated.
On the other hand, the blood level of the drug has been often tried to be stably maintained by enhancing the adhesive force of a patch itself to prevent peeling of the patch from the skin as much as possible. However, the adhesive force to a movable portion of the skin is insufficient. When the adhesive force is excessively enhanced, a pain occurs during peeling from the skin surface. Further, a possibility of causing skin irritation is also pointed out. Therefore, it is difficult that the percutaneous absorption of the drug is stably maintained over an application period only by simply enhancing the adhesive force of a plaster part.
In order to improve the applicability of a patch to the skin, a method of fixing a patch using a cover sheet (Patent Literature 1) and a reservoir-type patch preparation in which a cover sheet and a patch are integrated (Patent Literature 2) have been proposed.
In these patch preparations provided with the cover sheet, the cover sheet itself is not peeled and detached from an application portion of the skin due to a high adhesive force thereof. However, a patch part or a reservoir part cannot follow the movement of the application portion. Thus, the patch cannot be pressure-bonded to the skin. Therefore, stable drug release may not be achieved.
In particular, when in a patch containing a systemically active drug such as tulobuterol and fentanyl, the blood level of the drug cannot be stably maintained, the patch cannot exhibit a clear beneficial effect. Therefore, it is necessary that a whole patch preparation including a cover sheet part is always firmly adhered to the application portion of the skin. However, a patch satisfying these demands has not yet been developed.